Alzheimer's Disease - Research Directions

Research Directions

As of 2012, the safety and efficacy of more than 400 pharmaceutical treatments had been or were being investigated in 1012 clinical trials worldwide, and approximately a quarter of these compounds are in Phase III trials, the last step prior to review by regulatory agencies.

One area of clinical research is focused on treating the underlying disease pathology. Reduction of beta-amyloid levels is a common target of compounds (such as apomorphine) under investigation. Immunotherapy or vaccination for the amyloid protein is one treatment modality under study. Unlike preventative vaccination, the putative therapy would be used to treat people already diagnosed. It is based upon the concept of training the immune system to recognise, attack, and reverse deposition of amyloid, thereby altering the course of the disease. An example of such a vaccine under investigation was ACC-001, although the trials were suspended in 2008. Another similar agent is bapineuzumab, an antibody designed as identical to the naturally induced anti-amyloid antibody. Other approaches are neuroprotective agents, such as AL-108, and metal-protein interaction attenuation agents, such as PBT2. A TNFα receptor fusion protein, etanercept has showed encouraging results.

In 2008, two separate clinical trials showed positive results in modifying the course of disease in mild to moderate AD with methylthioninium chloride (trade name rember), a drug that inhibits tau aggregation, and dimebon, an antihistamine. The consecutive phase-III trial of dimebon failed to show positive effects in the primary and secondary endpoints.

The common herpes simplex virus HSV-1 has been found to colocate with amyloid plaques. This suggested the possibility that AD could be treated or prevented with antiviral medication.

Preliminary research on the effects of meditation on retrieving memory and cognitive functions have been encouraging. Limitations of this research can be addressed in future studies with more detailed analyses.

An FDA panel voted unanimously to recommend approval of florbetapir, which is currently used in an investigational study. The imaging agent can help to detect Alzheimer's brain plaques, but will require additional clinical research before it can be made available commercially.